Abstract Objective Prophylactic salpingo-oophorectomy is recommended to women who carry a BRCA1 or BRCA2 mutation to reduce the risks of breast, ovarian and fallopian tube cancer. We measured the ...impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual functioning in women with a BRCA mutation. Methods Women who underwent prophylactic salpingo-oophorectomy between October 1, 2002 and June 26, 2008 for a known BRCA1 or BRCA2 mutation were invited to participate. Participants completed questionnaires before prophylactic surgery and again one year after surgery. Measures of sexual functioning and menopausal symptoms before and after surgery were compared. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was evaluated. Results 114 women who underwent prophylactic surgery completed questionnaires before and one year after surgery. Subjects who were premenopausal at the time of surgery ( n = 75) experienced a significant worsening of vasomotor symptoms (hot flashes, night sweats and sweating) and a decline in sexual functioning (desire, pleasure, discomfort and habit). The increase in vasomotor symptoms and the decline in sexual functioning were mitigated by HRT, but symptoms did not return to pre-surgical levels. HRT decreased vaginal dryness and dyspareunia; however, the decrease in sexual pleasure was not alleviated by HRT. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy remained high regardless of increased vasomotor symptoms and decreased sexual function. Conclusions Women who undergo prophylactic salpingo-oophorectomy prior to menopause experience an increase in vasomotor symptoms and a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels.
Background Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Methods Women aged 75 years or younger ...with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m2 on day 1 and topotecan 0.75 mg/m2 on days 1–5, then four cycles of paclitaxel 175 mg/m2 over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. Results A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28–78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Conclusions Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.
In 2009, the Program in Evidence-based Care (pebc) of Cancer Care Ontario published a guideline on the follow-up of cervical cancer. In 2014, the pebc undertook an update of the systematic review and ...clinical practice guideline for women in this target population.
The literature from 2007 to August 2014 was searched using medline and embase extended to 2000 for studies of human papillomavirus (hpv) dna testing. Outcomes of interest were measures of survival, diagnostic accuracy, and quality of life. A working group evaluated the need for changes to the earlier guidelines and incorporated comments and feedback from internal and external reviewers.
One systematic review and six individual studies were included. The working group concluded that the new evidence did not warrant changes to the 2009 recommendations, although hpv dna testing was added as a potentially more sensitive method of detecting recurrence in patients treated with radiotherapy. Comments from internal and external reviewers were incorporated.
Follow-up care after primary treatment should be conducted and coordinated by a physician experienced in the surveillance of cancer patients. A reasonable follow-up strategy involves visits every 3-4 months within the first 2 years, and every 6-12 months during years 3-5. Visits should include a patient history and complete physical examination, with elicitation of relevant symptoms. Vaginal vault cytology examination should not be performed more frequently than annually. Combined positron-emission tomography and computed tomography, other imaging, and biomarker evaluation are not advocated; hpv dna testing could be useful as a method of detection of recurrence after radiotherapy. General recommendations for follow-up after 5 years are also provided.
CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin–pegylated liposomal doxorubicin (C–PLD) with carboplatin–paclitaxel (C–P) in patients with late-relapsing recurrent ...ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years.
Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m2 or 3-weekly C AUC 5 plus P 175 mg/m2 for six or more cycles.
One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C–PLD; 73 years, C–P; range 70–82 years) were included (n=71, C–PLD; n=86, C–P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P=0.005) but more grade ≥2 sensory neuropathy (P=0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C–PLD; 82%, C–P). In comparing arms within elderly patients, C–P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P<0.001 for all), severe leukopenia plus febrile neutropenia; C–PLD was associated with more grade ≥2 hand–foot syndrome (P=0.005). Median progression-free survival was 11.6 months (C–PLD) and 10.3 months (C–P; P=0.44).
Patients ≥70 years experienced more neuropathy, with a higher incidence in the C–P arm. Similar to all study patients, C–PLD provided a better therapeutic index with less toxicity than C–P in elderly women with platinum-sensitive ROC.
Abstract Introduction A cervical cytology based screening program is effective if there is regular screening of the ‘at risk’ population and close follow-up of those labeled abnormal. Methods This is ...a population cohort study of women between 20-69 year old who were eligible in Ontario from 2008-2010. We used administrative data to evaluate the rates of cervical cancer screening and follow-up of high grade Pap tests. Variation in cervical cytology coverage and follow-up of high grade abnormal results are associated with age, area level income and health region. Multivariate logistic regression was used to identify independent factors associated with screening and followup. Results 3.7 million women were eligible for screening of which 72% had a Pap smear in the prior 3 years. These rates varied by age, income and region (p < 0.0001). Women residing in the lowest income neighborhoods were half as likely to be screened (p < 0.0001). 83% of those with an high grade intraepithelial lesion Pap test result had follow-up with colposcopy or treatment within 6 months and this varied by year, age, income and region (p < 0.0001). Conclusions Despite universal health coverage, cervical cancer screening rates are suboptimal with older and low income women being at greatest risk. Follow-up among women with high grade abnormal tests is mediocre at 3 months and acceptable at 6 months. Novel models of cervical cancer screening program implementation are needed to address these inadequacies.
A system-level organizational guideline for gynecologic oncology was identified by a provincial cancer agency as a key priority based on input from stakeholders, data showing more limited ...availability of multidisciplinary or specialist care in lower-volume than in higher-volume hospitals in the relevant jurisdiction, and variable rates of staging for ovarian and endometrial cancer patients.
A systematic review assessed the relationship of the organization of gynecologic oncology services with patient survival and surgical outcomes. The electronic databases medline and embase (ovid: 1996 through 9 January 2015) were searched using terms related to gynecologic malignancies combined with organization of services, patterns of care, and various facility and physician characteristics. Outcomes of interest included overall or disease-specific survival, short-term survival, adequate staging, and degree of cytoreduction or optimal cytoreduction (or both) for ovarian cancer patients by hospital or physician type, and rate of discrepancy in initial diagnoses and intraoperative consultation between non-specialist pathologists and gyne-oncology-specialist pathologists.
One systematic review and sixteen additional primary studies met the inclusion criteria. The evidence base as a whole was judged to be of lower quality; however, a trend toward improved outcomes with centralization of gynecologic oncology was found, particularly with respect to the gynecologic oncology care of patients with advanced-stage ovarian cancer.
Improvements in outcomes with centralization of gynecologic oncology services can be attributed to a number of factors, including access to specialist care and multidisciplinary team management. Findings of this systematic review should be used with caution because of the limitations of the evidence base; however, an expert consensus process made it possible to create recommendations for implementation.
To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD carboplatin–pegylated liposomal doxorubicin (PLD) or CP ...(carboplatin–paclitaxel) in the CALYPSO trial.
CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety.
A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58–0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm).
Carboplatin–PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients.
The purpose of this guideline is to recommend systemic therapy options for women with recurrent epithelial ovarian cancer, including fallopian tube and primary peritoneal cancers.
This document ...updates the recommendations published in the 2011
guideline from Cancer Care Ontario. Draft recommendations were formulated based on evidence obtained through a systematic review of phase ii and iii randomized controlled trials (rcts). The draft recommendations underwent internal review by clinical and methodology experts, and external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline.
The primary literature search yielded thirty-six primary research papers representing thirty rcts that met the eligibility criteria. The guideline provides recommendations for patients with serous tumour histologies and with recurrent, platinum-resistant, and platinum-sensitive ovarian cancer.
The body of evidence from trials that included olaparib and bevacizumab consistently shows a benefit in progression-free survival (pfs) without a corresponding benefit in overall survival (os). The Working Group for this guideline designated pfs, which is associated with symptom control, as a critical outcome. A finding of net benefit can therefore be concluded based on significant differences in pfs. However, that benefit is not without identified harms. Given the identified harms, patient involvement in the decision-making process must take into consideration the side effect profiles of olaparib and bevacizumab within the context of improved pfs but minimal change in os.
What is the optimal chemotherapy treatment for women with recurrent ovarian cancer who have previously received platinum-based chemotherapy?
Currently, standard primary therapy for advanced disease ...involves a combination of maximal cytoreductive surgery and chemotherapy with carboplatin plus paclitaxel or with carboplatin alone. Despite initial high response rates, a large proportion of patients relapse, resulting in a therapeutic challenge. Because these patients are not curable, the goal of therapy becomes improvement in both quality and length of life. The search has therefore been to find active agents for women with recurrent disease following platinum-based chemotherapy.
Outcomes of interest included any combination of tumour response rate, progression-free survival, overall survival, adverse events, and quality of life.
The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. The systematic review and recommendations were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (DSG). The practice guideline was externally reviewed by a sample of practitioners from Ontario, Canada.
Thirteen randomized trials compared various chemotherapy regimens for patients with recurrent ovarian cancer. In five of the thirteen trials in which 100% of patients were considered sensitive to platinum-containing chemotherapy, further platinum-based combination chemotherapy significantly improved response rates (two trials), progression-free survival (four trials), and overall survival (three trials) when compared with single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these randomized trials compared the same chemotherapy regimens: carboplatin alone versus the combination of carboplatin and paclitaxel. Both trials were consistent in reporting improved survival outcomes with the combination of carboplatin and paclitaxel. In one trial, the combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. Median survival with carboplatin alone ranged from 17 months to 24 months in four trials. In eight of the thirteen trials in which 35%-100% of patients had platinum-refractory or -resistant disease, one trial reported a statistically significant 2-month improvement in overall survival with liposomal doxorubicin as compared with topotecan (15 months vs. 13 months, p = 0.038; hazard ratio: 1.23; 95% confidence interval: 1.01 to 1.50). In that trial, because of the limited clinical benefit and the unusual finding that a survival difference emerged only after a year of treatment with no corresponding improvement in the rate of response or of progression-free survival, the authors concluded that further confirmation by results from randomized trials were needed to establish the superiority of one agent over another in their trial. In one trial, topotecan was superior to treosulphan in patient progression-free survival by a span of approximately 2 months (5.4 months vs. 3.0 months, p < 0.001). Toxicity was reported in all of the randomized trials, and although data on adverse events varied by treatment regimen, the observed adverse events correlated with known toxicity profiles. As expected, combination chemotherapy was associated with higher rates of adverse events.
This clinical recommendation applies to women with recurrent epithelial ovarian cancer who have previously received platinum-based chemotherapy. Of specific interest are women who have previously shown sensitivity to platinum therapy and those who previously were refractory or resistant to platinum-based chemotherapy. As a general categorization within what is actually a continuum, "platinum sensitivity" refers to disease recurrence 6 months or more after prior platinum-containing chemotherapy, and "platinum resistance" refers to a response to platinum-based chemotherapy followed by relapse less than 6 months after chemotherapy is stopped. "Platinum-refractory disease" refers to a lack of response or to progression while on platinum-based chemotherapy.
Although the body of evidence that informs the clinical recommendations is based on randomized trial data, those data are incomplete. Based on the available data and expert consensus opinion, the Gynecology Cancer DSG makes these recommendations: Systemic therapy for recurrent ovarian cancer is not curative. It is therefore recognized that each patient must be individually assessed to determine optimal therapy in terms of recurrence, sensitivity to platinum, toxicity, ease of administration, and patient preference. All suitable patients should be offered the opportunity to participate in randomized trials, if available.In the absence of contraindications, combination platinum-based chemotherapy should be considered for patients with prior sensitivity to platinum-containing chemotherapy. As compared with carboplatin alone, the combination of carboplatin and paclitaxel significantly improved both progression-free and overall survival.If combination platinum-based chemotherapy is not indicated, then a single platinum agent should be considered. Carboplatin has demonstrated efficacy across trials and has a manageable toxicity profile.If a single platinum agent is not being considered, then monotherapy with paclitaxel, topotecan, or pegylated liposomal doxorubicin are seen as reasonable treatment options.Some patients may be repeatedly sensitive to treatment and may benefit from multiple lines of chemotherapy.For patients with platinum-refractory or platinum-resistant disease, the goals of treatment should be to improve quality of life by extending the symptom-free interval, by reducing symptom intensity, and by increasing progression-free interval, and, if possible, to prolong life.With non-platinum agents, monotherapy should be considered because no advantage appears to accrue to the use of non-platinum-containing combination chemotherapy in this group of patients. Single-agent paclitaxel, topotecan, or pegylated liposomal doxorubicin have demonstrated activity in this patient population and are reasonable treatment options.No evidence either supports or refutes the use of more than one line of chemotherapy in patients with platinum-refractory or platinum-resistant recurrence. Many treatment options have shown modest response rates, but their benefits over best supportive care have not been studied in clinical trials.
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